FTMG_ASPFM
ID FTMG_ASPFM Reviewed; 504 AA.
AC B9WZX6;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Fumitremorgin C monooxygenase {ECO:0000303|PubMed:19226505};
DE EC=1.14.14.119 {ECO:0000269|PubMed:19226505};
DE AltName: Full=Cytochrome P450 monooxygenase ftmP450-3 {ECO:0000303|PubMed:19226505};
DE AltName: Full=Fumitremorgin biosynthesis protein G {ECO:0000303|PubMed:23649274};
GN Name=ftmP450-3 {ECO:0000303|PubMed:19226505};
GN Synonyms=ftmG {ECO:0000303|PubMed:23649274};
OS Neosartorya fumigata (Aspergillus fumigatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Fumigati.
OX NCBI_TaxID=746128;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=BM939;
RX PubMed=19226505; DOI=10.1002/cbic.200800787;
RA Kato N., Suzuki H., Takagi H., Asami Y., Kakeya H., Uramoto M., Usui T.,
RA Takahashi S., Sugimoto Y., Osada H.;
RT "Identification of cytochrome P450s required for fumitremorgin biosynthesis
RT in Aspergillus fumigatus.";
RL ChemBioChem 10:920-928(2009).
RN [2]
RP FUNCTION.
RX PubMed=16000710; DOI=10.1099/mic.0.27962-0;
RA Grundmann A., Li S.M.;
RT "Overproduction, purification and characterization of FtmPT1, a
RT brevianamide F prenyltransferase from Aspergillus fumigatus.";
RL Microbiology 151:2199-2207(2005).
RN [3]
RP FUNCTION.
RX PubMed=16755625; DOI=10.1002/cbic.200600003;
RA Maiya S., Grundmann A., Li S.M., Turner G.;
RT "The fumitremorgin gene cluster of Aspergillus fumigatus: identification of
RT a gene encoding brevianamide F synthetase.";
RL ChemBioChem 7:1062-1069(2006).
RN [4]
RP FUNCTION.
RX PubMed=18683158; DOI=10.1002/cbic.200800240;
RA Grundmann A., Kuznetsova T., Afiyatullov S.S., Li S.M.;
RT "FtmPT2, an N-prenyltransferase from Aspergillus fumigatus, catalyses the
RT last step in the biosynthesis of fumitremorgin B.";
RL ChemBioChem 9:2059-2063(2008).
RN [5]
RP FUNCTION.
RX PubMed=19763315; DOI=10.1039/b908392h;
RA Steffan N., Grundmann A., Afiyatullov S., Ruan H., Li S.M.;
RT "FtmOx1, a non-heme Fe(II) and alpha-ketoglutarate-dependent dioxygenase,
RT catalyses the endoperoxide formation of verruculogen in Aspergillus
RT fumigatus.";
RL Org. Biomol. Chem. 7:4082-4087(2009).
RN [6]
RP FUNCTION.
RX PubMed=21105662; DOI=10.1021/ja106817c;
RA Jost M., Zocher G., Tarcz S., Matuschek M., Xie X., Li S.M., Stehle T.;
RT "Structure-function analysis of an enzymatic prenyl transfer reaction
RT identifies a reaction chamber with modifiable specificity.";
RL J. Am. Chem. Soc. 132:17849-17858(2010).
RN [7]
RP FUNCTION.
RX PubMed=23090579; DOI=10.1039/c2ob26149a;
RA Wollinsky B., Ludwig L., Xie X., Li S.M.;
RT "Breaking the regioselectivity of indole prenyltransferases: identification
RT of regular C3-prenylated hexahydropyrrolo[2,3-b]indoles as side products of
RT the regular C2-prenyltransferase FtmPT1.";
RL Org. Biomol. Chem. 10:9262-9270(2012).
RN [8]
RP FUNCTION, AND PATHWAY.
RX PubMed=23649274; DOI=10.1271/bbb.130026;
RA Kato N., Suzuki H., Okumura H., Takahashi S., Osada H.;
RT "A point mutation in ftmD blocks the fumitremorgin biosynthetic pathway in
RT Aspergillus fumigatus strain Af293.";
RL Biosci. Biotechnol. Biochem. 77:1061-1067(2013).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of fumitremorgins, indole alkaloids that
CC carry not only intriguing chemical structures, but also interesting
CC biological and pharmacological activities (PubMed:19226505,
CC PubMed:23649274). The biosynthesis of fumitremorgin-type alkaloids
CC begins by condensation of the two amino acids L-tryptophan and L-
CC proline to brevianamide F, catalyzed by the non-ribosomal peptide
CC synthetase ftmA (PubMed:16755625). Brevianamide F is then prenylated by
CC the prenyltransferase ftmPT1/ftmB in the presence of dimethylallyl
CC diphosphate, resulting in the formation of tryprostatin B
CC (PubMed:16000710, PubMed:21105662, PubMed:23090579). The three
CC cytochrome P450 monooxygenases, ftmP450-1/ftmC, ftmP450-2/ftmE and
CC ftmP450-3/FtmG, are responsible for the conversion of tryprostatin B to
CC 6-hydroxytryprostatin B, tryprostatin A to fumitremorgin C and
CC fumitremorgin C to 12,13-dihydroxyfumitremorgin C, respectively
CC (PubMed:19226505). The putative methyltransferase ftmMT/ftmD is
CC expected for the conversion of 6-hydroxytryprostatin B to tryprostatin
CC A (Probable). FtmPT2/FtmH catalyzes the prenylation of 12,13-
CC dihydroxyfumitre-morgin C in the presence of dimethylallyl diphosphate,
CC resulting in the formation of fumitremorgin B (PubMed:18683158).
CC Fumitremorgin B is further converted to verruculogen by ftmOx1/ftmF via
CC the insertion of an endoperoxide bond between the two prenyl moieties
CC (PubMed:19763315). In some fungal species, verruculogen is further
CC converted to fumitremorgin A, but the enzymes involved in this step
CC have not been identified yet (Probable). {ECO:0000269|PubMed:16000710,
CC ECO:0000269|PubMed:16755625, ECO:0000269|PubMed:18683158,
CC ECO:0000269|PubMed:19226505, ECO:0000269|PubMed:19763315,
CC ECO:0000269|PubMed:21105662, ECO:0000269|PubMed:23090579,
CC ECO:0000269|PubMed:23649274, ECO:0000305, ECO:0000305|PubMed:16000710}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=fumitremorgin C + 2 O2 + 2 reduced [NADPH--hemoprotein
CC reductase] = 12alpha,13alpha-dihydroxyfumitremorgin C + 2 H(+) + 2
CC H2O + 2 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:35967, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:72763,
CC ChEBI:CHEBI:72764; EC=1.14.14.119;
CC Evidence={ECO:0000269|PubMed:19226505};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:19226505,
CC ECO:0000269|PubMed:23649274}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AB436628; BAH24001.1; -; Genomic_DNA.
DR AlphaFoldDB; B9WZX6; -.
DR SMR; B9WZX6; -.
DR BioCyc; MetaCyc:MON-18766; -.
DR BRENDA; 1.14.14.119; 508.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:1902181; P:verruculogen biosynthetic process; IDA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alkaloid metabolism; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix; Virulence.
FT CHAIN 1..504
FT /note="Fumitremorgin C monooxygenase"
FT /id="PRO_0000424125"
FT TRANSMEM 12..32
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 442
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
SQ SEQUENCE 504 AA; 56823 MW; 72DBCE515778CF7D CRC64;
METLDAIQLP YLGVVGASLI VILGIILLFP LGSDPFITIN QHPRDLFQTK AKQQFEYNAA
ALLNEGLQTG HSAFRLVTNM VTYLILKDQY AEEIKNDSRF GAHEAVDPVL LVDLPGLESM
FQGSLHNQVP PMAVRALNKE LVHLTPSLSE EAMNCLQTRW TDSTEWHGVS IPETVLALIA
QMTTRALLGP ELCRNPEWLD IAKSFTTNRA IAVAAVQSWP SFLQPVIHWF LPPCRALRRQ
IQCARNIILP ALERERRAYC SDQPTKREFS NLVFIDQYAK GARYDATMAQ LRIIAVAFQT
TSDLVEKVIA RLCKHPELIE PLREEVVSVV GNRGLHRHSL RKLTLMESVM KETQRLEPAV
IIGMFRLAKE KVTLKDGTVV PKGTNIAFAN DLRFDPEMYL EPETFDGYRF QRMREDPAKI
DLAPFTKTRM SHLAFGHGKH ACPGRFLACD EAKLILCHIL LNYDIRAVEG SPPELRARGM
FVQLDPGAMM SVRRRRGTET APHG
